chr8-41269833-G-T

Variant names:

• chr8-41269833-G-T
• rs7013229
• NM_003012.5:c.623-4344C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003012.5(SFRP1):​c.623-4344C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,082 control chromosomes in the GnomAD database, including 8,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8908 hom., cov: 32)
• Consequence: SFRP1 NM_003012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 publications found

Genes affected

SFRP1 (HGNC:10776): (secreted frizzled related protein 1) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003012.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	NM_003012.5	MANE Select	c.623-4344C>A		intron	N/A	NP_003003.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.623-4344C>A		intron	N/A	ENSP00000220772.3	Q8N474
	SFRP1	ENST00000923189.1		c.545-4344C>A		intron	N/A	ENSP00000593248.1
	SFRP1	ENST00000379845.3	TSL:2	c.215-4344C>A		intron	N/A	ENSP00000369174.3	Q6ZSL4

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50805 AN: 151964 Hom.: 8909 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50845 AN: 152082 Hom.: 8908 Cov.: 32 AF XY: 0.329 AC XY: 24467 AN XY: 74346

African (AFR) AF: 0.316 AC: 13116 AN: 41458

American (AMR) AF: 0.260 AC: 3970 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3470

East Asian (EAS) AF: 0.0435 AC: 225 AN: 5178

South Asian (SAS) AF: 0.249 AC: 1200 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4070 AN: 10572

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25609 AN: 67974

Other (OTH) AF: 0.344 AC: 727 AN: 2114

Alfa AF: 0.345 Hom.: 3351

Bravo AF: 0.322

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.42
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7013229; hg19: chr8-41127352;